M. haemolytica is a gram negative bacterium normally found in the upper respiratory tract of healthy cattle, sheep and wild sheep. M. haemolytica descends into the lungs when cattle experience stress such as shipping, weaning, overcrowding, or viral infections and causes fibrinous and necrotizing bronchopneumonia, a chief component of the bovine respiratory disease complex (BRDC). Economic losses due to BRDC in North America is >$1 billion annually (Bowland and Shewen, 2000). M. haemolytica is the bacterium most commonly isolated from the lungs of cattle affected with BRDC. M. haemolytica serotype A1 is responsible for approximately 60% of shipping fever, whereas serotypes A6 and A2 account for 26% and 7% respectively (Al-Ghamdi et al., 2000; Purdy et al., 1997). Both M. haemolytica A1 and A6 account for >85% of BRDC cases involving bacterial pathogens.
The vaccines currently available in the market against M. haemolytica infections are only moderately protective against shipping fever of beef cattle but generally ineffective against neonatal dairy calf pneumonia (Virtala et al., 1996; Rice et al., 2007). The major cause of severe bacterial pneumonia in feedlot and neonatal dairy cattle is M. haemolytica serotype A1 followed by serotype A6 (Schreuer et al., 2000, Rice et al., 2007).
Experimental evaluation of all the commercial M. haemolytica A1 vaccines used in feedlot showed only partial protection in 50% of the studies (Perino and Hunsaker, 1997). Furthermore, cross-protection against M. haemolytica serotypes (either A6 or A2) has been difficult to achieve using conventional vaccine preparations (Purdy et al., 1993; Sabri et al., 2000). Therefore, an efficacious vaccine against M. haemolytica serotypes A1 and A6 could significantly improve dairy/beef production.
Effective immunity against M. haemolytica is multifaceted. Neutralizing Antibodies against exotoxin leukotoxin A (LktA) and surface antigens are necessary for protective immunity against M. haemolytica (Shewen and Wilkie, 1988). Due to the complex genetic machinery involved in controlling the expression of various M. haemolytica virulence factors, the specific surface antigens that are important in stimulating immunity have not been clearly determined (Lawrence et al, 2010). However, M. haemolytica outer membrane proteins (OMPs) have been implicated in stimulating immunity against surface antigens (Confer et al., 2003, Morton et al., 1995; Potter et al., 1999).
Intranasal immunization of cattle has been pursued for a while using bovine herpesvirus-1 (BoHV-1), bovine respiratory syncytial virus (BRSV) and infectious bovine rhinotracheitis virus (IBR) (Ellis et al., 2007; Muylkens et al., 2007). Commercially available Pfizer's INFORCE 3 when administered intranasally claims to prevent BRSV and also aids in the prevention of respiratory disease caused by IBR and bovine parainfluenza virus type 3 (PI3).
In an experimental study when a modified live leukotoxin deficient M. haemolytica mutant was administered intranasally in weaned beef feedlot calves, it resulted in reduced nasopharyngeal colonization with wild type M. haemolytica compared to non-vaccinated control calves (Frank et al., 2003). Although intranasal vaccination and leukotoxin deficient M. haemolytica are known, inventors are aware of no M. haemolytica vaccines successfully combining these concepts.